Chun-Fu Lai

Long-Term Risk of Coronary Events after AKI

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45 ml/min per 1.73 m(2). AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 1.7) [corrected] than patients with AKI but without CKD.The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge.

Pentoxifylline Attenuates Tubulointerstitial Fibrosis by Blocking Smad3/4-Activated Transcription and Profibrogenic Effects of Connective Tissue Growth Factor

Pentoxifylline (PTX) is a potent inhibitor of connective tissue growth factor (CTGF), but its underlying mechanism is poorly understood. Here, it was demonstrated that PTX inhibited not only TGF-beta1-induced CTGF expression but also CTGF-induced collagen I (alpha1) [Col I (alpha1)] expression in normal rat kidney fibroblasts (NRK-49F) and alpha-smooth muscle actin expression in normal rat kidney proximal tubular epithelial cells (NRK-52E). Furthermore, PTX attenuated tubulointerstitial fibrosis, myofibroblasts accumulation, and expression of CTGF and Col I (alpha1) in unilateral ureteral obstruction kidneys. The mechanism by which PTX reduced CTGF in NRK-49F and NRK-52E was investigated. Activation of Smad3/4 was essential for TGF-beta1-induced CTGF transcription, but PTX did not interfere with TGF-beta1 signaling to Smad2/3 activation and association with Smad4 and their nuclear translocation. However, PTX was capable of blocking activation of TGF-beta1-induced Smad3/4-dependent reporter as well as CTGF promoter, suggesting that PTX affects a factor that acts cooperatively with Smad3/4 to execute transcriptional activation. It was found that PTX increased intracellular cAMP and caused cAMP response element binding protein phosphorylation. The protein kinase A antagonist H89 abolished the inhibitory effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and forskolin recapitulated the inhibitory effect. In conclusion, these results indicate that PTX inhibits CTGF expression by interfering with Smad3/4-dependent CTGF transcription through protein kinase A and blocks the profibrogenic effects of CTGF on renal cells. Because of the dual blockade, PTX potently attenuates the tubulointerstitial fibrosis in unilateral ureteral obstruction kidneys.

Sleep Disturbance in Chronic Hemodialysis Patients: The Impact of Depression and Anemia

Background. Many patients with end-stage renal disease who are undergoing chronic hemodialysis suffer from sleep disturbance. This paper was designed to study the severity and prevalence of sleep disorders and the factors affecting the syndromes in this unique patient group. Methods. We conducted this study by the use of questionnaires. Included in this study were a total of 245 patients at our center who had end-stage renal disease (ESRD) and who received hemodialysis thrice weekly for more than three months. Their demographic data and biochemical and hematologic parameters were analyzed. All patients were asked to complete two questionnaires (in a Chinese version) of the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory second edition (BDI-II), either by themselves or with assistance from the medical staff. Results. One hundred and sixty-four patients completed both questionnaires with a response rate of 70.4%. Their mean age was 57.9 ± 11.8 (ranging from 23.1 to 83.7) years old. They had been receiving hemodialysis for an average of 49.1 ± 50.9 months before the study. The male to female ratio was 77:87. Seventy six (46.3%) patients had diabetes mellitus. The prevalence of sleep disturbance was 74.4% (122/164), defined as PSQI scores >5. The poor sleepers had higher BDI scores and a higher ratio of females comparing to the good sleepers. By a multivariate analysis, the BDI scores and female sex were the independent predictors of the patients being poor sleepers. In analyzing the poor sleepers, the BDI scores, durations of hemodialysis and hemoglobin levels were the independent factors for predicting the global PSQI scores. Conclusion. The questionnaire showed a high prevalence of insomnia in the dialytic population. The study also attributes a predictive role in sleep quality to gender, depression, dialytic duration, and hemoglobin levels. The data indicate that in the management of insomnia in this patient group, anemia and depression, both of which are potentially correctable, should be assessed.

Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury

IntroductionSepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.MethodsPatient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.ResultsAmong the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patients propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).ConclusionsUse of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

Relationship Between Periodontal Disease and Mortality in Patients Treated With Maintenance Hemodialysis

BACKGROUND The relationship between periodontitis and outcomes in patients treated with long-term hemodialysis is controversial. Our previous work suggests that periodontitis is associated with malnutrition and inflammation. Here, we hypothesize that periodontitis is associated with mortality in hemodialysis patients. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS 253 patients undergoing hemodialysis at a single hospital-based dialysis facility. PREDICTOR Severity of periodontal disease (mild, moderate, or severe based on oral examination of 6 teeth). OUTCOMES & MEASUREMENTS All-cause and cardiovascular mortality during a 6-year follow-up after an oral health examination of index teeth. RESULTS During the 6-year follow-up, 102 patients died. Death occurred in 70.6%, 41.8%, and 24.0% of patients with severe, moderate, and mild/no periodontitis, respectively. Using mild/no periodontitis as the reference group and adjustment for demographic characteristics, comorbid conditions, and selected laboratory values, HRs for all-cause mortality were 1.39 (95% CI, 0.83-2.34) and 1.83 (95% CI, 1.04-3.24) for moderate and severe periodontitis, respectively. HRs for cardiovascular mortality were not statistically significant. LIMITATIONS Single assessment of periodontal disease severity. CONCLUSIONS For patients undergoing long-term hemodialysis, periodontitis is associated with increased risk of death. Clinical trials are required to determine whether treatment of periodontitis decreases mortality.

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury.

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients.

Nasal Carriage of Methicillin-resistant Staphylococcus aureus Is Associated with Higher All-Cause Mortality in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage is a recognized risk factor for subsequent endogenous infections. However, the association between MRSA carriage and patient survival in hemodialysis patients has not been established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In March 2007, this prospective cohort study enrolled 306 outpatients under maintenance hemodialysis from a hospital-based dialysis center in Taiwan. They received two consecutive weekly nasal swab cultures at the beginning of the study. Patients having at least one positive culture of MRSA were defined as MRSA carriers. Subjects were followed up until December 31, 2008. The primary outcome was all-cause mortality. Main secondary outcomes were infection-related mortality and morbidity. RESULTS We identified 29 MRSA carriers (9.48%) at study entry. After a median of 613 days of follow-up, Kaplan-Meier analysis showed significant survival differences between MRSA carriers and noncarriers (log-rank P = 0.02). Compared with noncarriers, MRSA carriers had a 2.46-fold increased risk of dying from any cause, after adjusting for covariates at the start of follow-up. The adjusted hazard ratios of infection-related mortality and occurrence of subsequent S. aureus infection in carriers were 4.99 and 4.31, respectively. CONCLUSIONS A major limitation is the relatively small sample size of MRSA carriers. Nevertheless, we demonstrated that there may be an association between MRSA nasal carriage and poor clinical outcomes in an outpatient hemodialysis population. This underscores the need for routine surveillance of MRSA nasal carriage and should alert the physicians of a group at high risk of morbidity and mortality.

Verification and evaluation of aldosteronism demographics in the Taiwan Primary Aldosteronism Investigation Group (TAIPAI Group)

Objective: Current data on primary aldosteronism (PA) from Asian populations are scarce. This cohort study clarifies the attributes of patients with PA in a typical Chinese population. Design: An observational cohort study. Methods: The records of patients referred to the Hypertension Clinic from a multi-centre registration in Taiwan from January 1995 to December 2007 were reviewed. All patients with PA were classified into two subtypes: aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA); their characteristics were compared. Results: Our cohort consisted of 346 patients with PA, 255 with APA and 91 with IHA. The initial hypokalaemia (59% in APA vs. 27.5% in IHA, p < 0.0001) and transtubular potassium gradient (TTKG) (6.30 ± 2.41 in APA vs. 4.91 ± 2.03 in IHA, p = 0.01) were higher in the APA group. Baseline plasma aldosterone concentration (PAC) was also significantly different between the two subgroups (49.96 ± 38.15 ng/dl in APA vs. 34.24 ± 21.47 in IHA, p < 0.0001). Conclusions: In typical Chinese PA patients, the APA subgroup had a higher proportion of hypokalaemia with elevated TTKG and higher PAC as compared with the IHA subgroup. This largest Asian database also demonstrated major differences between the Caucasian and Chinese populations including female predilection, frequent hypokalaemia, and common paralytic myopathy.

Association of uraemic pruritus with inflammation and hepatitis infection in haemodialysis patients

BACKGROUND Chronic inflammation and hepatitis C virus (HCV) infection have been implicated in the pathogenesis of uraemic pruritus in haemodialysis (HD) patients. However, each ones independent roles have not been previously studied. METHODS A total of 321 HD patients diagnosed with end-stage renal disease with maintenance HD for >3 months were included. A visual analogue scale (VAS) was used to subjectively measure the severity of itching. Based on the VAS score, patients were divided into three groups: Group 1, no pruritus (VAS = 0); Group 2, mild to moderate pruritus (VAS 0-5) and Group 3, severe pruritus (VAS >5). RESULTS There were 120 (37.4%) patients without any pruritus, 141 (43.9%) with mild to moderate pruritus and 60 (18.7%) with severe pruritus. Forty-six (14.3%) had hepatitis B virus (HBV) infection and 37 (11.5%) had hepatitis C virus (HCV) infection. The average serum high-sensitivity C-reactive protein (hsCRP) level was 0.58 mg/dl. Patients with severe pruritus had a significantly higher serum hsCRP level and more HBV or HCV infection (all P < 0.05). In the multi-variable logistic regression model, higher levels of hsCRP (OR = 3.54, P = 0.008) and HCV infection (OR = 2.77, P = 0.014) were both significant independent predictors for severe pruritus. CONCLUSION Our study demonstrated the heavy burden of pruritus in HD patients and corroborated the role of inflammation in the pathogenesis of uraemic pruritus. HCV infection is associated with severe uraemic pruritus but is independent of the serum hsCRP level in HD patients.